The well-known technique of electrospray ionization is used in mass spectrometry to generate free ions. The conventional electrospray process involves breaking the meniscus of a charged liquid formed at the end of the capillary tube into fine droplets using an electric field. In conventional electrospray ionization, a liquid is pushed through a very small charged capillary. This liquid contains the analyte to be studied dissolved in a large amount of solvent, which is usually more volatile than the analyte. An electric field induced between the capillary electrode and the conducting liquid initially causes a Taylor cone to form at the tip of the tube where the field becomes concentrated. Fluctuations cause the cone tip to break up into fine droplets which are sprayed, under the influence of the electric field, into a chamber at atmospheric pressure in the presence of drying gases. An optional drying gas, which may be heated, may be applied so as to cause the solvent in the droplets to evaporate. According to a generally accepted theory, as the droplets shrink, the charge concentration in the droplets increases. Eventually, the repulsive force between ions with like charges exceeds the cohesive forces and the ions are ejected (desorbed) into the gas phase. The ions are attracted to and pass through a capillary or sampling orifice into the mass analyzer.
Incomplete droplet evaporation and ion desolvation can cause high levels of background counts in mass spectra, thus causing interference in the detection and quantification of analytes present in low concentration. It has been observed that smaller initial electrospray droplets tend to be more readily evaporated and, further, that droplet sizes decrease with decreasing flow rate. Thus, it is desirable to reduce the flow rate per emitter and, consequently, the droplet size, as much as possible (on the order of microliters or even nanoliters per minute) in order to spectra with minimal background interference. However, conventional electrospray devices and conventional liquid chromatography apparatuses which deliver eluent to such electrospray devices are typically associated with flow rates of several microliters per minute up to 1 ml per minute. It is therefore of interest to use assembly or array of multiple nanospray or microspray emitters with the goal to generate more ions per unit volume of analyte solvent while still realizing low flow rates per each emitter.
Attempts have been made to manufacture an electrospray device which produces nanoelectrospray. For example, Wilm and Mann, Anal. Chem. 1996, 68, 1-8 describes the process of electrospray from fused silica capillaries drawn to an inner diameter of 2-4 μm at flow rates of 20 mL/min. Specifically, a nanoelectrospray at 20 mL/min was achieved from a 2 μm inner diameter and 5 μm outer diameter pulled fused-silica capillary with 600-700 V at a distance of 1-2 mm from the ion-sampling orifice of an API mass spectrometer. Other nano-electrospray devices have been fabricated from substantially planar substrates with microfabrication techniques that have been borrowed from the electronics industry and microelectromechanical systems (MEMS), such as chemical vapor deposition, molecular beam epitaxy, photolithography, chemical etching, dry etching (reactive ion etching and deep reactive ion etching), molding, laser ablation, etc.
In order to realize the aforementioned benefits of micro-electrospray or nano-electrospray at higher overall flow rates, electrospray arrays of densely packed tubes or nozzles have been developed, using either capillary pulling or microfabrication and MEMS techniques, so as to increase the overall flow rate without affecting the size of the ejected droplets. For example, FIG. 1A illustrates an array of fused-silica capillary nano-electrospray ionization emitters arranged in a circular geometry, as taught in United States Patent Application Publication 2009/0230296 A1, in the names of Kelly et al. Each nano-electrospray ionization emitter 2 comprises a fused silica capillary having a tapered tip 3. As taught in United States Patent Application Publication 2009/0230296 A1, the tapered tips can be formed either by traditional pulling techniques or by chemical etching and the radial arrays can be fabricated by passing approximately 6 cm lengths of fused silica capillaries through holes in one or more discs 1. The holes in the disc or discs may be placed at the desired radial distance and inter-emitter spacing and two such discs can be separated to cause the capillaries to run parallel to one another at the tips of the nano-electrospray ionization emitters and the portions leading thereto.
In order to introduce ions generated by a multi-emitter electrospray apparatus into a mass spectrometer (MS), the simplest approach would be to locate the several emitters at sufficient distances from one other such that electric fields from any given emitter do not measurably affect the operation of any other emitter and provide a separate ion inlet into the mass spectrometer for each emitter. This approach is not generally practical because of the requirement of proportionally higher evacuation pumping speed with an increase in the number of emitters and ion inlets. A preferable approach is to use a standard vacuum interface (single ion inlet to the mass spectrometer, such as the entrance orifice of the ion transfer tube) while locating and configuring the emitters in such a way that the transmission efficiency into the single ion inlet is close to optimized. Normally, a liquid jet with charged droplets emanating from an emitter tip occupies space roughly represented by cone with an 80-90 degree angle at the apex (at the emitter tip). The optimal emitter position, relative to an MS ion inlet, is therefore a compromise between the competing requirements of efficient sample transfer into the ion inlet and efficient sample de-solvation. To accomplish efficient sample transfer, the distance between the emitter capillary and the ion inlet should be short and the axis of the emitter should be directed towards the ion inlet. On the other hand, to accomplish efficient de-solvation, a longer travel distance to the inlet is required. For a single emitter, the optimal distance is found to be between 2 to 4 mm, resulting in a 4-8 mm diameter ion plume at the inlet plane.
The above considerations suggest that, if multiple electrospray emitters are employed instead of a single emitter, these should all be positioned as close as possible to the position of the single emitter that they replace. Unfortunately, placing muliple emitters in random stack or arranged in regular pattern in the rather limited volume near the vacuum interface has had limited success, in practice. One of the reasons for such limited success is the interference of the electric fields originating from the various emitters, when packed into the requisite small space. This effect has been theoretically modeled by Si et al. (“Experimental and theoretical study of a cone-jet for an electrospray microthruster considering the interference effect in an array of nozzles”, Journal of Aerosol Science 38, 2007, pp. 924-934) who demonstrated that, for an array of closely-spaced emitters operating simultaneously, the operating voltage required for cone jet spraying increases as the emitter spacing decreases. Regele et al. (“Effects of capillary spacing on EHD spraying from an array of cone jets”, Journal of Aerosol Science 33, 2002, pp. 1471-1479) experimentally determined similar results for an array of four electrospray capillaries and mathematically predicted the same behavior for a 5×5 square array. Regele et al. also found that, at very close spacings (3-4 capillary diameters), the electric potential required for stable electrospray operation can decrease and postulated that fine wire electrodes interspersed among the capillaries could improve operation. Also, space charge clouds produced by individual cone jets contribute to interference effects.
Recently, Deng et al. (“Compact multiplexing of monodisperse electrosprays”, Journal of Aerosol Science 40, 2009, pp. 907-918) have described a microfabricated planar nozzle array system, schematically illustrated in FIG. 1B, capable of being fabricated with a packing density of up to 11,547 sources/cm2. The Deng et al. apparatus (FIG. 1B) comprises a reservoir 4 used to distribute an analyte bearing liquid to an array of electrospay nozzles 5, held at an electric potential V1, so as to form Taylor cones 6 and emit jets through apertures in a separate planar extractor electrode 7, held at a second electric potential V2. The apertures in the extractor electrode 7 are aligned with respective nozzles 5 and the gap between the extractor electrode and the nozzle tips is comparable to the nozzle diameter and spacing. The apparatus further comprises a collector electrode 8 held at a potential V3. The applied potentials are such that V1>V2>V3 (with V3 typically being ground potential). Deng et al. note that the extractor electrode 7 both localizes the electric field and shields the jet region (between the nozzles 5 and the extractor electrode 7) from the spray region (between the extractor electrode and the collector electrode 8).
In FIG. 2, interference effects between emitters of a conventional emitter array are shown based on distortion in equipotential (iso-electric potential) surface shapes when multiple emitters present. Each of FIGS. 2A-2C is a cross section through a conventional electrospray apparatus comprising one or more emitter capillary electrodes 10a-10c, and a counter electrode 12, 14, 16 comprising one or more apertures 11a-11e through which emitted ions pass on a path to a mass spectrometer ion inlet. Solid arrows in FIG. 2 represent calculated ion trajectories for m/z=+508 ions emitted in a cone with 25 degrees semi angle. Dashed lines in FIG. 2 represent calculated equipotential surfaces at 250 Volt intervals. These calculations were performed using SIMION 3-D, version 8.0.4 ion optics modeling software (available from Scientific Instrument Services of Ringoes, N.J.). The calculations employed a 2 dimensional grid with 200 grid units per millimeter around electrospray emitter capillaries having inner diameters of 100 μm, outer diameters 230 μm and energized at 2.0 kiloVolt, 3.0 mm away from a grounded counter electrode. The spacing between emitter capillaries was set at 2.5 mm. FIGS. 2A, 2B and 2C show the calculated results for the case of a single emitter, three emitters in a line and five emitters in a line, respectively. The dashed lines shown in FIGS. 2A-2C represent the intersection of three dimensional iso-potential surfaces with the cross-sectional plane of the diagrams.
The calculated results presented in FIGS. 2A-2C clearly demonstrate that attempts to place emitters in close mutual proximity (for instance, with an inter-emitter distance close to or smaller than the emitter—inlet distance) result in off-axis deflection of ions emitted from peripheral emitters, thereby possibly leading to decreased transmission efficiency into a mass spectrometer. Further, the electric field at the outermost emitters is stronger relative to the field at the central or innermost emitters. Because of the variation of electric field strength across the array, electrospraying conditions will be different for the different emitters. The different electrospray conditions may include non-uniformity of rates of emission among a plurality of emitters, non uniformity of direction of emitted particles among the various emitters, and even non-uniformity in kinetic energy of emitted ions comprising a single mass-to-charge ratio (m/z). These inconsistencies may possibly causing inconsistent or noisy experimental results.
Although the apparatus described by Deng et al. (FIG. 1B) appears to perform adequately in many situations, the present inventors have determined that the planar extractor electrode utilized in that apparatus does not provide the optimal shielding between the separate electrospray emitters of an array. Thus, the present invention addresses the need for an optimized shield electrode configuration.